Assessing cachexia in obesity: contradiction or perfectly possible?

PURPOSE OF REVIEW: Existing definitions of clinically important weight loss in patients with cancer do not specifically address weight loss in patients who are obese at presentation. This review explores the clinical impact of weight loss and depletion of the skeletal muscle mass (i.e., criteria defining cancer cachexia), in patients with obesity. RECENT FINDINGS: Overweight and obese BMI values are shown by many recent studies to pose a survival advantage in patients with cancers of advanced stage, when compared with BMI in normal and underweight ranges. The classification of cancer-associated weight loss has evolved, and current grading schemes evaluate the impact of weight across the range of BMI values. Weight loss is associated with mortality in patients with BMI more than 30 kg/m 2 , however this is to a much lesser degree than in patients with lower BMI values. Diagnostic imaging permits the precise assessment of skeletal muscle index (SMI) in patients with cancer, and it has been clearly shown that while usually quite muscular, obese patients can have profound muscle depletion (i.e., sarcopenia), independent of the presence of weight loss. Muscle depletion associates strongly with mortality in obese patients, as well as with complications of cancer surgery and systemic therapy. SUMMARY: It would seem contradictory to diagnose concurrent obesity and cachexia, as these terms represent opposite ends of the weight spectrum. Weight loss can occur in anyone with cancer, however its priority for clinical management may be lesser in obese versus low body weight individuals. Sarcopenic obesity is strongly associated with a poor clinical outcome and deserves further research, diagnosis in clinical practice, and new strategies for mitigation.

Associations of nutrition impact symptoms with depression in patients with advanced cancer.

PURPOSE: Advanced cancer patients have nutrition impact symptoms (NISs), while many of them have depressive moods. This study aimed to determine the associations of NISs with depression. METHODS: This study was a secondary analysis. The dietary intake and 19 NISs in patients receiving palliative care were evaluated using 10-point scales, and the patients were categorized into two groups (non-depression and depression groups) using the cutoff based on the Patient Health Questionnaire-9 (PHQ-9). To determine associations between depression and the number of NISs with a score of ≥ 4, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. RESULTS: A total of 225 participants were divided into the non-depression group (n = 148) and the depression group (n = 77). The prevalence of depression was 34.2%. Dietary intake was lower, and the number of NISs with a score of ≥ 4 was higher in the depression group (both p < 0.001). All NISs were more severe in the depression group. Significant differences were observed in 15 of the 19 NISs. In the logistic regression model, significantly higher adjusted ORs were observed in the groups with 4-6 NISs and 7 or more NISs with a score of ≥ 4 (10.76 [95% CI, 2.07-55.91], p = 0.016; 17.02 [95% CI, 3.08-94.22], p < 0.001) than in the group with no NISs with a score of ≥ 4. CONCLUSION: Having four or more NISs with a score ≥ 4 was associated with depression.

Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer.

BACKGROUND & AIMS: There is no definition of nutrition impact symptoms (NISs) in cancer care. Moreover, there is a lack of evidence on the associations of NISs with dietary intake and eating-related distress (ERD) in advanced cancer. Therefore, this study aimed to determine the associations of NISs with dietary intake and ERD in patients with advanced cancer. METHODS: This study entailed a secondary analysis of a multicenter self-reported questionnaire designed to develop measurements that assess ERD experienced by patients. Participants evaluated their dietary intake and 19 symptoms regarded as NISs using a 10-point scale. To determine the association between dietary intake and the number of NISs with a score ≥4, estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. Furthermore, to assess the association between ERD and the number of NISs with a score ≥4, multiple regression analysis was performed. RESULTS: A total of 302 patients were included in the analysis. The higher the number of NISs with a score ≥4, the lower the dietary intake tended to be. In the logistic regression model, significantly higher adjusted ORs than in the no NISs with a score ≥4 group were observed in the 4-6 NISs group, 7-9 NISs group, and 10 or more group (0.19 [95% CI, 0.07-0.52], p = 0.001; 0.11 [95% CI, 0.03-0.42], p = 0.001; 0.07 [95% CI, 0.01-0.36], p = 0.002, respectively). In the multiple regression analysis, the number of NISs with a score ≥4 was identified as one of the factors significantly associated with ERD. CONCLUSIONS: Having 4 or more NISs with a score ≥4 was shown to be predictive of the likelihood of reduced dietary intake. Furthermore, the higher the number of NISs with a score ≥4, the more likely the eating-related quality of life was impaired in advanced cancer.

Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Body weight and composition endpoints in cancer cachexia clinical trials: Systematic Review 4 of the cachexia endpoints series.

Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.

Holistic multimodal care for patients with cancer cachexia and their family caregivers.

Patients with cancer cachexia frequently suffer from physical symptoms and psychological symptoms of illness, which can lead to emotional distress in patients and family caregivers. Although there is no standard care to manage cancer cachexia despite its high prevalence and negative impact on quality of life in patients and family caregivers, there is accumulating evidence showing the importance of holistic multimodal care for cancer cachexia. However, there is no agreement on the essential components of holistic multimodal care. Therefore, the aims of this review are to give an overview of what is known about the holistic multimodal care and to suggest the composition of a multidisciplinary team to achieve holistic interventions. Holistic multimodal care for cancer cachexia is defined as an approach that addresses physical health through medical, pharmacological, nutritional, and rehabilitative interventions as well as psychological, emotional, and social well-being issues according to the needs of patients and family caregivers. Moreover, an ideal multidisciplinary team is proposed to achieve holistic interventions based on patient- and family-centered care. However, the development of educational programs on cancer cachexia for both clinicians and patients and family caregivers is needed. Furthermore, measurements to assess the benefits of holistic multimodal care also need to be established.

TITAN Trial: A Randomized Controlled Trial of a Cardiac Rehabilitation Care Model in Breast Cancer.

Background: Cardiac rehabilitation (CR) modeled care is recommended for patients with breast cancer to mitigate risk of cardiotoxicity. However, the cardiovascular impact of CR-modeled interventions has not been studied. Objectives: The purpose of this study was to evaluate if a multidisciplinary model of CR reduces cardiotoxicity and improves cardiovascular risk in patients undergoing breast cancer treatment. Methods: We randomly assigned patients with stage I to III breast cancer scheduled to receive anthracycline and/or trastuzumab-based chemotherapy to the CR intervention (n = 37) or usual care (n = 37). The intervention included guideline-directed management of cardiovascular risk factors, dietary counselling, and supervised exercise for 52 weeks. Cardiac magnetic resonance imaging, cardiopulmonary exercise testing, dual-energy x-ray absorptiometry, and serum biomarkers were acquired at baseline and 52 weeks. Results: There was no difference in the primary outcome, left ventricular ejection fraction (LVEF), between groups at 52 weeks (61% ± 6%). Other markers of cardiotoxicity, including high-sensitivity troponin I and brain natriuretic peptide, were similar between groups. However, total cholesterol (5.2 ± 0.8 mmol/L to 4.7 ± 0.8 mmol/L, P = 0.002) and low-density lipoprotein (3.0 ± 0.7 mmol/L to 2.4 ± 0.7 mmol/L, P < 0.001) decreased in the intervention group at 52 weeks and were unchanged in usual care. In all patients, adverse cardiac and metabolic changes occurred over 52 weeks including reductions in LVEF, left ventricular mass, high-density lipoprotein, lean body mass, insulin-like growth factor-1, as well as increased triglycerides, whole-body and truncal fat mass (all P < 0.050). Conclusions: The CR-modeled intervention had no effect on LVEF or biomarkers of cardiotoxicity. Future lifestyle intervention trials in patients with breast cancer should consider targeting other risk factors associated with incident cardiovascular disease. (Multidisciplinary Team IntervenTion in CArdio-ONcology [TITAN Study] [TITAN]; NCT01621659).